Testicular Torsion Research Articles

Protective effects of Passiflora Incarnata on ischemia-reperfusion injury in testicular torsion: an experimental study in a rat model

Protective effects of Passiflora Incarnata on ischemia-reperfusion injury in testicular torsion: an experimental study in a rat model

Sequential Administration of Febuxostat, Amlodipine and Vitamin E Attenuate Oxidative Stress and Improve Spermatogenesis in Testicular Ischemia Reperfusion Injury in Wistar Rats

This study investigated the effects of sequential administration of febuxostat, amlodipine, and vitamin E on oxidative stress and spermatogenesis following testicular ischemia-reperfusion injury (TIRI) in Wistar rats. Ninety male rats (120-150 g) were divided into 9 groups (n=10 each): sham operation (SO), torsion-detorsion (TD), and seven treatment groups receiving different combinations of the drugs. The treatment groups included torsion + febuxostat + detorsion (TFD), torsion + detorsion + amlodipine (TDA), torsion + detorsion + vitamin E (TDV), and combinations thereof (TFDA, TFDV, TDAV, TFDAV). TIRI was induced by 720° clockwise testicular torsion for 1 hour followed by detorsion. Febuxostat (5 mg/kg) was administered 30 minutes after torsion, amlodipine (2.5 mg/kg) immediately upon detorsion, and vitamin E (10 mg/kg) 30 minutes after detorsion. Rats were sacrificed 56 days post-reperfusion. Testicular tissue was analyzed for antioxidant enzymes (superoxide dismutase, catalase), lipid peroxidation (malondialdehyde), total protein, inflammatory markers (serum nitrite, IL-1β), and spermatogenesis indices (testicular biopsy score, Leydig cell count). Results showed that TIRI significantly decreased antioxidant enzymes, significantly increased lipid peroxidation and inflammatory markers, and impaired spermatogenesis. In the TD group, superoxide dismutase (SOD) and catalase (CAT) activities were significantly decreased, while malondialdehyde (MDA) increased significantly compared to the SO group (p<0.01). Serum nitrite and IL-1β levels in the TD group were also increased (p<0.001). Furthermore, the testicular biopsy score and Leydig cell count in the TD group were significantly decreased in this study (p<0.01). Sequential administration of febuxostat, amlodipine and vitamin E, particularly when all three were used (TFDAV group), significantly attenuated these changes. In the TFDAV group, SOD and CAT activities were improved, while MDA decreased compared to the TD group (p<0.05). Serum nitrite and IL-1β levels in the TFDAV group were also decreased (p<0.001). In addition, the testicular biopsy score and Leydig cell count in the TFDAV group increased in comparison with the TD group (p<0.001). The study concludes that this sequential multi-drug approach shows promise in mitigating the long-term detrimental effects of TIRI on testicular function and fertility. The combination of febuxostat (a xanthine oxidase inhibitor), amlodipine (a calcium channel blocker), and vitamin E (an antioxidant) appears to provide protection against oxidative stress and inflammation induced by TIRI, thereby preserving spermatogenesis.

Reducing time from presentation to surgical intervention for testicular torsion: implementation of a quality improvement protocol

IntroductionTimely surgical intervention for patients with testicular torsion is a quality benchmark set by the U.S. News and World Report (USNWR) for pediatric urology. In this study, we describe and evaluate a quality improvement initiative to reduce the time to surgical intervention for testicular torsion at a single institution through the implementation of a clinical care pathway called “code torsion.”MethodsData abstraction was performed through retrospective chart review to assess process measures. Patients <21 years old with testicular torsion requiring surgical intervention were included. The clinical protocol “code torsion” was created by a multidisciplinary quality improvement workgroup with the primary goal of reducing the time from emergency department presentation to surgical intervention for testicular torsion. “Code torsion” was implemented in October 2021, which was assessed in addition to subsequent interventions through plan–do–study–act (PDSA) cycles.ResultsA total of 30 patients were identified prior to “code torsion” implementation and 14 thereafter. The mean time from triage to operating room (OR) was 228 min prior to “code torsion” compared with 180 min after protocol implementation (p = 0.047). The proportion of cases that had surgical intervention within the 4-h USNWR metric increased from 63% pre-protocol to 93% post-protocol (p = 0.07). Of the patients, 40% required orchiectomy prior to “code torsion” compared with 29% after implementation (p = 0.5). Patients requiring orchiectomy had a significantly longer time from symptom onset to surgical intervention (87 vs. 9.8 h, p < 0.001).ConclusionImplementation of the protocol “code torsion” was successful in reducing the time from presentation to surgical intervention for testicular torsion. The rates of testicular salvage did not differ after “code torsion” implementation and were instead found to be dependent on the total ischemia time.

Predictive factors for manual detorsion success in testicular torsion.

In cases of testicular torsion (TT), prompt diagnosis and treatment are highly associated with organ salvage, and manual detorsion (MD) is a recommended maneuver as a first intervention. In our study, we aimed to investigate the effect of predictive factors of TT in predicting the success of MD. A retrospective, 2-center study was conducted on patients diagnosed with TT between January 2015 and 2024. Demographic, clinical, ultrasound, and laboratory characteristics at presentation were analyzed. MD was routinely performed as the first intervention in all patients. Predictive parameters were compared in the MD success and failure groups. Univariate and multiple logistic regression analysis was used to identify risk factors for MD failure. A total of 94 patients were included in the study. The median age of the patients was 20 (IQR: 12-69) years, and the median symptom duration was 6 (IQR: 4-12) hours. MD confirmed by Doppler ultrasonography was successful in 52 (55.3%) patients and unsuccessful in 42 (44.7%). Age, symptom duration, Testicular Workup for Ischemia and Suspected Torsion (TWIST) score, TWIST risk groups, WBC, neutrophil, monocyte counts, and Monocyte/Eosinophil ratio (MER) were statistically different between the two groups. In multiple logistic regression analysis, the risk factors for failure of MD were found to be being over 18years of age, the duration of symptoms being longer than 9h, and MER > 28. Current urology guidelines suggest that age, symptom duration, and MER are reliable predictors of the success of MD, which is recommended in all cases of TT.

Proanthocyanidin alleviates testicular torsion/detorsion-induced ischemia/reperfusion injury in rats

Testicular torsion is an urological emergency and can lead to ischemia damage and testicular loss if not diagnosed in time. Proanthocyanidin is reported to have anti-inflammatory and antioxidant properties. The current study aimed to examine the possible effects of proanthocyanidin (P) on the testis in torsion/detorsion (T/D)-induced testicular ischemia/reperfusion (I/R) injury in rats. Forty rats were divided into four groups (n=10 for each): sham-operated (sham), I/R, I/R + P100 (100 mg/kg, 30 min before torsion), and I/R + P200 (200 mg/kg, 30 min before torsion). Testicular T/D was performed on the left testicle by 3 hours of torsion at 720° clockwise, followed by 3 hours of detorsion. In the I/R group, an increase in malondialdehyde (MDA) levels and a decrease in glutathione (GSH), vitamin C (Vit C), glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD) values were determined compared to the sham group (p<0.001). Moreover, an increase in the expression of cleaved caspase-3 and Bcl2-associated X protein (Bax), a decrease in the expression of B-cell lymphoma 2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) were detected in the I/R group (p<0.001). Histopathologically, it was determined that the Johnsen and Cosentino scores of the testicles were irregular in the I/R group (p<0.001). Proanthocyanidin treatment caused a decrease in MDA, cleaved caspase-3 and Bax levels and an increase in GSH, Vit C, GPx, G6PD, Bcl-2 and PCNA values. Additionally, Johnsen and Cosentino rearranged the scores. The present findings revealed the protective and curative effects of proanthocyanidin in organ damage due to testicular torsion/detorsion-induced ischemia/reperfusion with their antioxidative and antiapoptotic properties.

An update on the endocrine manifestations of antiphospholipid syndrome.

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.

Commentary to the ball's in your court: Trends, causes, outcomes, and costs of patient transfer for pediatric testicular torsion

Commentary to the ball's in your court: Trends, causes, outcomes, and costs of patient transfer for pediatric testicular torsion

The Role of Hematologic Parameters in Predicting Orchiectomy for Testicular Torsion

The Role of Hematologic Parameters in Predicting Orchiectomy for Testicular Torsion

Хірургічні ускладнення пурпури Шенляйн-Геноха в дітей

Henoch-Schönlein purpura is the systemic pathology that affected the small vessels of the skin, gastrointestinal tract, kidneys, and joints. Typical clinical manifestation of Henoch-Schönlein purpura include palpable purpura, abdominal pain syndrome, arthralgia, renal involvement, and, in some children, externa genitalia involvement. The aim of this study was to present the own experience in the management of three children with the surgical complications of Henoch-Schönlein purpura. The own experience includes three children with Henoch-Schönlein purpura, particularly two children with ileum intussusception (both of 3 years old) and one patient of 4 years old with the syndrome “acute scrotum”. Gastrointestinal involvement may appear in most of patients with Henoch-Schönlein purpura and intussusception is the most common complication, which require the urgent treatment. Appearance of typical palpable purpura followed the abdominal pain syndrome and ultrasonography is the main method of diagnostic in this group of patients. Ileum and ileocolic are the common types of intussusception in children with Henoch-Schönlein purpura. The main method of treatment in case of ileum intussusception is surgical reduction, while in case of ileocolic intussusception non-surgical reduction can be applied. Besides the typical manifestation of Henoch-Schönlein purpura, in some children could be the scrotal involvement, which developing after appearance of palpable purpura, and rare caused by inflammation or torsion of testis or hydatid. It is believed that patients with Henoch-Schönlein purpura and scrotal involvement have more severe clinical course when compared with patients with abdominal manifestation, which agreed with our observation. Conclusions. In children older than one year, with the abdominal pain, with or without bloody stools, and ultrasonographic signs of intussusception, it is necessary consider about possibility the presence of Henoch-Schönlein purpura in these patients. In children with Henoch-Schönlein purpura despite the corticosteroids’ treatment, could be developed the syndrome of “acute scrotum”, which required emergent surgery. The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the institution mentioned in the work. Informed consent of the patients was obtained for the research. No conflict of interests was declared by the authors.

Evaluation of effects of Tempol on testicular ischemia/reperfusion injury

AimTempol, a synthetic antioxidant compound, has received significant attention for its potential therapeutic applications in recent years, especially against ischemia/reperfusion (I/R) injury. The aim of the present research was to assess the protective effects of Tempol on testicular I/R injury caused by testicular torsion and detorsion (T/D) in rats. MethodsThe subjects were divided into five groups: sham, testicular T/D, testicular T/D with Tempol treatment at 50 and 100 mg/kg, and healthy rats treated with Tempol at 100 mg/kg. Testicular torsion was induced by rotating the left testicles for 2 h, followed by detorsion for 24 h. Testicular tissues were evaluated for gene expression, oxidative stress markers, and histopathology, epididymal sperms were stained and analyzed, and blood serum samples were collected to measure the testosterone hormone. ResultsThe results showed that testicular I/R caused a significant decrease in sperm velocity parameters, viability, and count, as well as an increase in abnormal sperms (p < 0.05). However, treatment with Tempol significantly improved these parameters (p < 0.05). Histopathological analysis revealed severe damage to the testicular tissues, but treatment with Tempol improved the structural integrity of the seminiferous tubules. Testicular I/R also resulted in increased oxidative stress index and decreased testosterone levels significantly (p < 0.05), but Tempol administration mitigated these effects significantly (p < 0.05). Furthermore, the expression of Bax and Bcl2, genes associated with apoptosis, were significantly altered by testicular I/R (p < 0.05), but Tempol prevented these changes significantly (p < 0.05). ConclusionThese findings provide strong evidence that Tempol can effectively prevent testicular I/R injury.

Delayed Presentation of Testicular Torsion: A Case Report

Testicular torsion is a medical emergency due to twisting of spermatic cord on its axis which hinders blood supply to the testes, causing acute symptoms. It is considered one of the emergency presentations seen in young adolescents. This emergency is mostly observed in patients under 18 years of age, and occurs is 3.8 per 100000 population. We describe a 25-year-old patient presenting to the emergency department with acute symptoms typical of testicular torsion. Keywords: Testicular torsion, twisting of spermatic cord.

Recidiverende testiculaire torsie 27 jaar na eerdere orchidopexie: casusbespreking

Recurrent testicular torsion 27 years after previous orchidopexy: a case report A recurrent testicular torsion after a previous orchidopexy is a rare phenomenon that requires a high index of suspicion to avoid misdiagnosis and delayed treatment. This case intends to emphasize the importance of considering a recurrent testicular torsion in the differential diagnosis of acute scrotal pain, regardless of the patient’s age. The case involves a 45-year-old man with a history of a bilateral testicular fixation for a testicular torsion at the age of 18. The patient presented with recurrent testicular pain, despite the fact that both testes previously had been fixed to the scrotal wall. This case illustrates that a recurrent testicular torsion can manifest even when the testis is fixed to the scrotal wall. This emphasizes the importance of including a recurrent testicular torsion in the differential diagnosis of acute scrotal pain. Furthermore, during the surgical intervention particular attention should be given to ensuring a proper fixation of both testes using non-absorbable sutures at a minimum of 2 points to reduce the risk of a recurrent torsion. A recurrent testicular torsion following a previous orchidopexy is a rare condition that requires vigilance in case of acute scrotal pain. This case report reinforces the need for a thorough examination and emphasizes the importance of safe testicular fixation during surgery to minimize the risk of recurrence. The threshold for surgical exploration should always be kept low, even after a previous orchidopexy.

Establishment of a rabbit model of different degrees of testicular torsion

Introduction and objectivesDifferent degrees of testicular torsion result in varying degrees of testicular damage, which influences treatment options and outcomes. Therefore, establishing a testicular torsion model with different degrees is necessary for clinical diagnosis. Materials and methodsRabbits were randomly divided into four groups and their spermatic cords were twisted at 0 °, 180 °, 360 °, and 720 °, respectively. Color Doppler flow imaging (CDFI) were performed to evaluate the blood supply in testicles. The twisted testicles were surgically removed at six hours post-operation and were evaluated by morphological observation and Hematoxylin and Eosin staining. ResultsCDFI signals were gradually decreased as the degree of testicular torsion increased, and scores of CDFI in the 360 ° and 720 ° groups were significantly decreased at postoperative six hours compared to pre-surgery. Compared to the sham, the testicle in the 180 ° group exhibited slight congestion, whereas the testicles in the 360 ° and 720 ° groups were dark red in color and had severe congestion and unrecognizable vessels. Hematoxylin and Eosin staining showed mild spermatogenic cell reduction and testicular interstitial hemorrhage in the 180 ° group. In the 360 ° and 720 ° groups, disordered seminiferous tubules, shed spermatogenic cells in tubules, inflammatory cell infiltration, and severe hemorrhage were found. In comparison with the sham, interstitial hemorrhage scores in the 360 ° and 720 ° groups were significantly higher, and scores of germinal epithelial cell thickness in the three testicular torsion groups were significantly decreased. ConclusionsCollectively, we successfully constructed a testicular torsion model with different degrees in rabbits.

Activation of SIRT1/Nrf2/HO-1 and Beclin-1/AMPK/mTOR autophagy pathways by eprosartan ameliorates testicular dysfunction induced by testicular torsion in rats

Testicular torsion carries the ominous prospect of inducing acute scrotal distress and the perilous consequence of testicular atrophy, necessitating immediate surgical intervention to reinstate vital testicular perfusion, notwithstanding the paradoxical detrimental impact of reperfusion. Although no drugs have secured approval for this urgent circumstance, antioxidants emerge as promising candidates. This study aspires to illustrate the influence of eprosartan, an AT1R antagonist, on testicular torsion in rats. Wistar albino rats were meticulously separated into five groups, (n = 6): sham group, eprosartan group, testicular torsion-detorsion (T/D) group, and two groups of T/D treated with two oral doses of eprosartan (30 or 60 mg/kg). Serum testosterone, sperm analysis and histopathological examination were done to evaluate spermatogenesis. Oxidative stress markers were assessed. Bax, BCL-2, SIRT1, Nrf2, HO-1 besides cleaved caspase-3 testicular contents were estimated using ELISA or qRT-PCR. As autophagy markers, SQSTM-1/p62, Beclin-1, mTOR and AMPK were investigated. Our findings highlight that eprosartan effectively improved serum testosterone levels, testicular weight, and sperm count/motility/viability, while mitigating histological irregularities and sperm abnormalities induced by T/D. This recovery in testicular function was underpinned by the activation of the cytoprotective SIRT1/Nrf2/HO-1 axis, which curtailed testicular oxidative stress, indicated by lowering the MDA content and increasing GSH content. In terms of apoptosis, eprosartan effectively countered apoptotic processes by decreasing cleaved caspase-3 content, suppressing Bax and stimulating Bcl-2 gene expression. Simultaneously, it reactivated impaired autophagy by increasing Beclin-1 expression, decreasing the expression of SQSTM-1/p62 and modulate the phosphorylation of AMPK and mTOR proteins. Eprosartan hold promise for managing testicular dysfunction arising from testicular torsion exerting antioxidant, pro-autophagic and anti-apoptotic effect via the activation of SIRT1/Nrf2/HO-1 as well as Beclin-1/AMPK/mTOR pathways.

Testicular Traction Technique with Intact Cremasteric Reflex, a Novel Approach for Manual Detorsion: Case Report.

Recognizing testicular torsion is extremely important in patients presenting to the emergency department (ED) with acute scrotal pain. Traditional manual detorsion techniques are frequently employed by emergency physicians but are not always successful. Delays in detorsion increase the risk of testicular infarction and infertility, and the need for orchiectomy. Novel techniques such as the testicular traction technique have been described as a potential solution for difficult-to-detorse testicles. Our case report describes a 20-year-old male with no significant past medical history who presented to a rural ED with acute, atraumatic testicular pain secondary to testicular torsion with an intact cremasteric reflex. After confirming the diagnosis using Doppler ultrasound, manual detorsion using the traditional "open book" technique was attempted and unsuccessful. The patient was subsequently successfully detorsed using the novel testicular traction technique. The testicular traction technique is a safe, rapid, and effective primary or adjunctive technique in manual testicular detorsion. Given the time-sensitive nature of testicular torsions, adjunctive techniques play a crucial role in managing challenging detorsions, particularly in resource-limited rural settings with limited access to urologic services. Although it is commonly thought that the cremasteric reflex is absent in testicular torsions, it may be present in rare circumstances, and its presence should not be an absolute in ruling out torsion.

An Uncommon Cause of Testicular Infarct: A Case Report and Review of the Literature of Testicular Infarcts From Laparoscopic Inguinal Hernia Repair

BackgroundTesticular ischemia requires timely diagnosis and definitive management to avoid serious consequences such as orchiectomy. It is almost always caused by testicular torsion; however, there are other causes to be aware of. Case ReportA 32-year-old man developed testicular ischemia following a laparoscopic robotic-assisted inguinal hernia repair with preperitoneal mesh. The ischemia progressed to a fully infarcted testicle with no evidence of torsion on subsequent surgical exploration. He ultimately did require an orchiectomy. Why should an Emergency Physician be aware of this?While extremely rare, testicular ischemia or infarct must be considered in patients presenting with testicular pain shortly after inguinal hernia repair. Emergent surgical evaluation and loosening of the hernia mesh may be required to salvage the testicle.

Standardizing male pelvic anatomy teaching using a clinical enrichment video.

Evolving trends in medical education and modern curricular changes have reduced the amount of time and resources allocated for anatomy education. As the amount of dedicated anatomy education time decreases, more self-directed learning is required. Cadaveric dissection and didactic teaching have been supplemented with multimedia, clinical anatomy, and imaging for over 20 years, with mixed results. Specifically, the use of video-based anatomy teaching increases medical learning, if done methodically. A 20-minute video was produced highlighting surgical anatomy using the following operative cases: perineal anatomy (artificial urinary sphincter case), inguinal and testicular anatomy (scrotal orchidopexy for acute testicular torsion), prostate anatomy (robotic radical prostatectomy), and bladder anatomy (endoscopy). The annotated video was shown to first-year medical students. Pre- and post-video multiple choice question quizzes were given to the students. Once submitted, the students completed a survey. Overall, 191 first-year medical students participated in our study. Average scores were similar between each quiz (50±16% vs. 49±17%) and there was no statistically significant change. Seventy-seven percent of participants felt the video improved their knowledge of urologic anatomy and 83% agreed the video should be shown to future classes. Sixty percent of participants felt the video solidified their anatomy knowledge, 78% felt the video was stimulating and entertaining, and 43% of the students felt the video increased their interest in pursuing urology as a career choice. Anatomy teaching can be supplemented using surgical videos, especially in a time when in-person anatomy teaching is limited. Further study is required to determine whether this teaching modality improves long-term anatomy knowledge retention.

Rare case of testicular abnormality in a 17-year-old adolescent boy

Polyorchism is a rare congenital anomaly defined as the incidence of more than two testicles. This pathology is considered to be extremely rare and may remain asymptomatic for a long time. The disease is detected predominantly during the examination of other urologic pathologies such as inflammation, hydrocele, testicular torsion, inguinal hernia, male infertility, and malignant changes. The reported case of polyorchism was confirmed during surgery for left testicular hydatid torsion in a 17-yearold boy. The abnormal testis had its own tunica vaginalis testis, epididymis, common deferent duct, and shared blood supply with the left testis. The testes were preserved during surgery. No impaired spermatogenesis was detected in the patient.

Protective effects of Passiflora Incarnata on ischemia-reperfusion injury in testicular torsion: an experimental study in a rat model.

The current study aimed to explore the potential protective effect of Passiflora Incarnata L., (PI) in treating IR injury after testicular torsion in rats. This research investigated the impact of PI on IR damage in male Wistar albino rats. Animals were divided to three groups: group 1 (sham), group 2 (IR), and group 3 (IR+PI). The malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels did not significantly differ across the groups (p = 0.830, p = 0.153 and p=0.140, respectively). However, Group 3 demonstrated a superior total antioxidant status (TAS) value compared to Group 2 (p = 0.020). Concurrently, Group 3 presented a significantly diminished mean total oxidant status (TOS) relative to Group 2 (p = 0.009). Furthermore, Group 3 showed a markedly improved Johnsen score relative to Group 2 (p < 0.01). IR caused cell degeneration, apoptosis, and fibrosis in testicular tissues. PI treatment, however, mitigated these effects, preserved seminiferous tubule integrity and promoted regular spermatogenesis. Furthermore, it reduced expression of tumor necrosis factor-alpha (TNF-α), Bax, and Annexin V, signifying diminished inflammation and apoptosis, thereby supporting cell survival (p < 0.01, p < 0.01, p < 0.01, respectively). This study revealed that PI significantly reduces oxidative stress and testicular damage, potentially benefiting therapies for IR injuries.

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury.

Testicular torsion is a critical urologic condition for which testicular detorsion surgery is considered irreplaceable as well as the golden method of reversal. However, the surgical treatment is equivalent to a blood reperfusion process, and no specific drugs are available to treat blood reperfusion injuries. Salidroside (SAL) is one of the main effective substances in rhodiola, which has been shown to have antioxidant and antiapoptosis activities. This study was designed to determine whether SAL exerted a protective effect on testicular ischemia-reperfusion (I/R) injury. In this study, the I/R injury model of the testes and reoxygenation (OGD/R) model were used for verification, and SAL was administered at doses of 100mg/kg and 0.05mmol/L, respectively. After the experiments, the testicular tissue and TM4 Sertoli cells were collected for histopathologic and biochemical analyses. The results revealed that SAL improves the structure of testicular tissue and regulates the oxidation-antioxidation system. To further understand the molecular mechanisms of SAL in treating testicular I/R injuries, transcriptomics and metabonomics analyses were integrated. The results show that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway is enriched significantly, indicating that it may be the main regulatory pathway for SAL in the treatment of testicular I/R injuries. Thereafter, transfection with Nrf2 plasmid-liposome was used to reverse verify that the Nfr2/HO-1/GPX4/ferroptosis signaling pathway was the main pathway for SAL anti-testicular I/R injury treatment. Thus, it is suggested that SAL can protect against testicular I/R injuries by regulating the Nfr2/HO-1/GPX4 signaling pathway to inhibit ferroptosis and that SAL may be a potential drug for the treatment of testicular I/R injuries.